DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Priority
The instant application is a 371 of PCT/US2023/012091 filed on 02/01/2023, which claims domestic benefit to US provisional application no. 63/305,804 filed on 02/02/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/18/2023, 06/14/2023, 02/05/2025, and 10/16/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Claims
The preliminary claim amendments filed on 04/15/2023 are acknowledged. Claims 1, 4, 6, 9, 12, and 16-17 are amended.
Accordingly, claims 1-20 are pending and being examined on the merits herein.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3 and 5 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
There is insufficient antecedent basis for the limitations “first therapeutic agent cargo” and “second therapeutic agent cargo” in claims 3 and 5 because claim 1 (claims 3 and 5 depend from claim 1) recites “at least one of R1, R2, and R3 is a therapeutic agent cargo”, making it unclear which of the first and second therapeutic agent cargo is referring back to the recited “at least one of R1, R2, and R3 is a therapeutic agent cargo”. Furthermore, it is unclear if claims 3 and 5 are indicating that both of the first and second therapeutic agent cargos are required, or if just one of the recited first and second therapeutic agent cargo is required.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 5, 8, 11, and 14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 5, 8, 11, and 14 recite “wherein the efficacy of the … therapeutic agent cargo is enhanced.”.
Here, the instant claims recite a functional limitation of therapeutic agent cargos that are enhanced by the recited sophorolipid (compound of formula I). The disclosure, however, does not identify a representative number of therapeutic agent cargo species within the claimed genus for performing the claimed function, nor does the disclosure provide a structure-function relationship which
would allow one of ordinary skill in the art to identify which therapeutic agent cargos would have the claimed function.
MPEP 2173.05(g) states that “A claim term is functional when it recites a feature ‘by what it
does rather than by what it is’” and that “Unlimited functional claim limitations that extend to all means
or methods of resolving a problem may not be adequately supported by the written description or may
not be commensurate in scope with the enabling disclosure, both of which are required by 35 U.S.C.
112(a) and pre-AIA 35 U.S.C. 112, first paragraph.
Applicant provides exemplary compounds of their invention on pages 31-35, which shows different combinations of therapeutic agent cargos attached to the sophorolipid structure (compound of formula I) at the R1, R2, or R3 position. Applicant shows that the attached therapeutic agent cargo can be salicylic acid, butyric acid, beta-hydroxybutryic acid, phosphoric acid, glutamine, and succinic acid in any combination at these positions.
However, Applicant does not demonstrate which therapeutic agent cargos are enhanced. Applicant only indicates that their modified sophorolipid structures are capable of efficiently delivering a therapeutic agent cargo to the target site (see page 3 lines 16-19) and that the therapeutic agent cargo may be released by hydrolysis and/or by the action of enzymes such as lipases (see page 10 lines 30-35). Furthermore, Applicant indicates that a therapeutic agent cargo is any suitable molecule having a hydroxyl, carboxyl, inorganic acid, and/or amine group such that it is capable of forming an ester or amide linkage with the sophorolipid structure at the defined linkage points in the recited formula (I) structure (see page 10 lines 28-30). Therefore, the instant specification does not provide a representative number of species to cover the recited “enhanced” effect for the recited therapeutic agent cargo. There are no examples in the instant specification to demonstrate a structure-function relationship which would allow a skilled artisan to predict which therapeutic agent cargo would result in being enhanced by the compound of formula I.
The state of the prior art discloses that it is not entirely predictable how conjugate modifications such as amino acid conjugation to sophorolipids will affect its bioactivity. For example, Azim (in IDS filed 05/18/2023) discloses that sophorolipids and their derivatives have shown immense potential as therapeutic agents that can function as septic shock antagonists, anticancer agents, and antibacterial, antiviral, spermicidal, and antifungal agents. However, more structural derivatives of sophorolipids are needed to better define structural-biological activity relationships and thereby enhance SL efficacy and its spectrum of action (see second paragraph left column page 1523).
Azim demonstrates that among the alkyl esters of amino acid conjugated sophorolipids tested, the ethyl ester of leucine conjugate was most active and was most effective against Moraxella sp., S. sanguinis, and M. imperial (see third paragraph left column page 1528). Azim further discloses that the ethyl ester leucine conjugates were more potent against Moroaxella sp. than a monoacetylated ethyl ester (MAEE) sophorolipid conjugate, however the MAEE sophorolipid conjugate was higher against the other microorganisms tests (see third paragraph left column page 1528). Therefore, Azim concludes that more experiments are needed to determine how acetylating the sophorose head groups of amino acid conjugates modulates the biological properties of the conjugate (see right column page 1528).
Here, Azim demonstrates that it is not entirely predictable to determine the structure function of any suitable molecule having a hydroxyl, carboxyl, inorganic acid, and/or amine group such that it is capable of forming an ester or amide linkage with the sophorolipid structure because Azim shows that various amino acid conjugated sophorolipids had differences in the activity against different species of bacteria, and further discloses that more experimentation is necessary to further elucidate which structures modulates the biological properties of the sophorolipid conjugates. Therefore, it is also unpredictable to further determine which of these molecules would then be enhanced by the sophorolipid structure.
Furthermore, Zerkowski (in IDS filed on 02/05/2025) discloses that the structural multiplicity of sophorolipids complicates attempts to correlate molecular shape with surfactant behavior (see first paragraph right column page 57). Zerkowski demonstrates in Fig. 1 on page 58 the conjugation of sophorolipids to various amino acid groups as shown in Scheme 1 on page 60. Even though Zerkowski teaches these conjugates displayed good surfactant properties based on the critical micelle concentration (CMC) and surface tension values, Zerkowski notes that certain properties such as ionization state of an aggregated state of the SL micelle is difficult to predict due to the proximity of neighboring charges and that the acid-based chemistry of micellar surfactants cannot be described by using a single value for the pKa (see right column page 61).
Here, Zerkowski also demonstrates that it is not entirely predictable to determine the structure function of any suitable molecule having a hydroxyl, carboxyl, inorganic acid, and/or amine group such that it is capable of forming an ester or amide linkage with the sophorolipid structure because Zerkowski teaches that there are difficulties in characterizing the functional properties of various amino acid conjugated sophorolipids.
Therefore, it is not evident by the disclosure or the prior art, that the Applicant was in
possession of a representative number of species of therapeutic agent cargos that would be enhanced by the compound of formula I. Furthermore, as discussed above, there is no disclosed or art recognized correlation between structure and function which would allow for the predictable identification of therapeutic agent cargos that would be enhanced. Therefore, the instant claim does not meet the written description requirement under 35 USC 112(a).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5, 8, 11, and 14 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 5, 8, 11, and 14 recite “wherein the efficacy of the … therapeutic agent cargo is enhanced.”.
If Applicant were to argue that the 112a rejection for instant claims 5, 8, 11 and 14 discussed above is unreasonable because the enhancement is a necessary result of the therapeutic agent cargo being attached to the sophorolipid, then these instant claims would not further limit the subject matter of the claim upon which it depends, since the recited “enhanced” limitation would be an inherent feature of the recited compound.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 3, and 6-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Azim et al. (Bioconjugate Chem., 2006 in IDS filed 05/18/2023).
Azim teaches amino acid conjugated sophorolipids (see Abstract).
Azim teaches the following conjugates shown in Scheme 1 on page 1524 and below:
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Here, compound 10 meets the limitation of the recited compound of formula (I) in instant claim 1 because compound 10 of Azim has Y is methyl, R1 is a serine (amino acid) that is conjugated via an amide linkage, R2 and R3 are H, and n=13 with one unsaturated double bond.
In regards to instant claim 3, this claim further limits what the first and second therapeutic agent cargo can be, however claim 1 (claim 3 depends from claim 1) only requires one therapeutic agent cargo on the compound as recited “wherein at least one of R1, R2, and R3 is a therapeutic agent cargo”. Therefore, neither claim 3 nor claim 1 limit the compound to having more than one therapeutic agent, so the compound 10 of Azim, which teaches one therapeutic agent cargo, meets the limitations of claim 3.
Therefore, claims 1, 3, and 6-7 are anticipated.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Azim et al. (Bioconjugate Chem., 2006 in IDS filed 05/18/2023).
The teachings of Azim are as described and teach the compound recited in instant claim 1. Furthermore, Azim demonstrates in Table 1 on page 1528 that their conjugates had antibacterial activity against both gram positive and negative organisms (see Abstract).
Even though Azim does not demonstrate administering their conjugates to a subject, it would have been prima facie obvious before the effective filing date of the claimed invention to have administered the conjugates of Azim to a subject in order reduce pathogenic gram-negative bacteria in the microbiome of the subject because Azim demonstrates that their conjugates had antibacterial activity against gram negative organisms.
Claim(s) 2 is rejected under 35 U.S.C. 103 as being unpatentable over Azim et al. (Bioconjugate Chem., 2006 in IDS filed 05/18/2023), as applied to claim 1, and further in view of Salek et al. (Front. Bioeng. Biotechnol., published 01/27/2022 in PTO-892).
The teachings of Azim are as described above and teach the compound recited in claim 1.The difference between Azim and the claimed invention is that Azim does not teach n is 12.
Salek teaches the physicochemical characteristics of several glycolipid surfactants of microbial origin (see Abstract). Specifically, Salek teaches that the production of sophorolipids depends on the selected strain and various growth parameters (see second paragraph left column page 7). Salek teaches that the carbon length of the fatty acid chain moiety on the sophorolipid can vary such C6, C9, C16, and C18 based on the selection of a hydrophobic carbon source (see second paragraph left column page 7 through second paragraph right column page 7). Here, the C16 fatty acid chain disclosed in Salek meets the limitation of n=12 because the fatty acid chain length moiety in the recited compound of formula (I) would be a C16 fatty acid chain when n=12.
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the fatty acid chain length on the sophorolipid of Azim to be a C16 fatty acid chain as disclosed in Salek to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Salek provides guidance that the fatty acid chain length can be modified during the production of the sophorolipid. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of fatty acid chain lengths on the sophorolipid with a reasonable expectation of success.
Claim(s) 9-10 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Azim et al. (Bioconjugate Chem., 2006 in IDS filed 05/18/2023), as applied to claim 1 above, and further in view of Zerkowski et al. (Journal of Surfactants and Detergents, 2006 in IDS filed on 02/05/2025).
The teachings of Azim are as described above and teach the compound recited in claim 1. Furthermore, Azim teaches that biosurfactants represent an emerging class of important compounds in biomedical science that offer antifungal, antibacterial, antimycoplasmal, and antiviral properties, and further teaches that the proposed primary mechanism of action of these surfactants is membrane lipid order perturbation, which comprises the viability of microorganisms (see first paragraph under section “Biological Activity” left column page 1528).
The difference between Azim and the claimed invention is that Azim does not teach at least one of R2 and R3 is the second therapeutic agent cargo.
Zerkowski teaches amino acid – glycolipid conjugates using carbodiimide-mediated coupling methods (see Abstract). Zerkowski teaches the glycolipid used was a stearic sophoroside, and the aim of their study was to modify the sophorolipid to increase its water solubility as well as to introduce sites at the polar head groups that permitted further chemical derivatization (see Abstract). Zerkowski teaches that their goal was to examine ways in which the fundamental sophorolipid skeleton could be chemically modified to increase its utility as a surfactant, and in particular append amino acid groups (see third paragraph right column on page 57).
Zerkowski demonstrates the synthesis of their amino acid – glycolipid conjugates using a Paba linker in FIG. 1 on page 58 and shown below:
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Here, the R1 group in the conjugate structure can be any one of the protected amino acid groups as shown in Scheme 1 on page 60. Furthermore, the conjugate structure shown above demonstrates conjugation of an amino acid at the R2 position of the instant compound formula (I) and further demonstrates an amino acid conjugated via an ester linkage because the Paba linker used forms an ester linkage between the sophorolipid and the amino acid.
Zerkowski further demonstrates in Fig. 3 on page 61 and Table 1 on page 61 that the amino acid-conjugated sophorolipids displayed good surfactant properties with critical micelle concentration values being clustered in the range of high 10−6 to low 10−5 M, and minimum surface tension values being below 40mN m−1 (see Abstract).
It would have been prima facie obvious before the effective filing date of the claimed invention to have further modified the amino acid conjugated sophorolipids of Azim by further attaching an additional amino acid at the R2 position using an ester linkage as demonstrated in Zerkowski to arrive at the claimed invention. One of ordinary skill would have been motivated to make this modification with a reasonable expectation of success because Azim provides guidance of using sophorolipids as anti-microbial agents due to its biosurfactant properties, and Zerkowski provide guidance of modifying these sophorolipids to increase its utility as a surfactant by conjugating an amino acid group on the R2 using via Paba linker (ester linkage). Therefore, an ordinary skilled artisan could have predictably considered conjugating the R2 position with an amino acid as demonstrated in Zerkowski, and would have been further motivated to do so in order to increase its surfactant properties.
In regards to instant claims 12-13, it would have also been prima facie obvious before the effective filing date of the claimed invention to make the R1 position of the sophorolipid as disclosed in the combined teachings of Azim and Zerkowski described above unmodified to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Zerkowski provides guidance of amino acid – sophorolipid conjugates that are only modified at the R2 position. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of amino acid modification sites with a reasonable expectation of success.
Claim(s) 1, 4, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Imura et al. (Journal of Oleo Science in IDS filed on 05/18/2023) in view of Zerkowski et al. (Journal of Surfactants and Detergents, 2006 in IDS filed on 02/05/2025)
Imura teaches the spontaneous vesicle formation from the sodium salt of acidic sophorolipid (SLNa) and its potential application as a skin penetration enhancer for triterpene glycosides extracted from the fruits of Siraitia grosvenorii Swingle (see Abstract). Imura teaches that bio-based surfactants are natural amphiphiles that are abundantly produced from a variety of renewable resources by microorganisms and have received great attention because of their unique properties, including bio-degradability, low toxicity, and versatile biological functions, compared to petroleum-based surfactants (see left column page 141).
Imura teaches the structure of their sodium salt sophorolipids in Fig 1 on page 142 and shown below:
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Imura teaches that vesicle formulations have recently attracted attention to enhance transdermal absorption of active ingredients (see first paragraph under section “In vitro skin permeation study” right column on page 144). Imura demonstrates in Fig. 5 on page 145 that the SLNa vesicles acted as a penetration enhancer for an active ingredient.
The difference between Imura and the claimed invention is that Imura does not teach their sophorolipid having a therapeutic agent cargo such as an amino acid.
The teachings of Zerkowski are described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the sodium salt of acidic sophorolipid disclosed in Imura by attaching an amino acid via a Paba linker (ester linkage) at the R2 position as demonstrated by Zerkowski to arrive at the claimed invention. One of ordinary skill would have been motivated to make this modification with a reasonable expectation of success because Imura provides guidance of using sophorolipids as a skin penetration enhancer due to its biosurfactant properties, and Zerkowski provide guidance of modifying these sophorolipids to increase its utility as a surfactant by conjugating an amino acid group on the R2 using a Paba linker (ester linkage). Therefore, an ordinary skilled artisan could have predictably considered conjugating the R2 position with an amino acid as demonstrated in Zerkowski, and would have been further motivated to do so in order to increase its surfactant properties.
In regards to instant claim 15, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered the modified sophorolipid as disclosed by the combined teachings of Imura and Zerkowski described above to a subject to improve the dermal penetrability of an active ingredient as demonstrated in Imura to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Imura demonstrates that their sophorolipids can be used as a skin penetration enhancer for an active ingredient.
Claim(s) 1, 5-6, 8-9, 11-12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Azim et al. (Bioconjugate Chem., 2006 in IDS filed 05/18/2023) in view of Zerkowski et al. (Journal of Surfactants and Detergents, 2006 in IDS filed on 02/05/2025), Nowak et al. (ChemMedChem, 2021 in PTO-892), and Imura et al. (Journal of Oleo Science in IDS filed on 05/18/2023).
The teachings of Azim are as describe above and teach the compound recited in instant claims 1 and 6 as discussed above. The combined teachings of Azim and Zerkowski are as described above and teach the compound recites in instant claims 1, 9, and 12.
The references, however, do not teach wherein the efficacy of the first and/or second therapeutic agent cargos is enhanced.
Nowak teaches antibacterial agents based on amino acid scaffold (see Abstract). Nowak teaches that the amino acid skeleton is of a crucial importance for their antimicrobial activity, since very often they are structural analogs of amino acid intermediates of different microbial biosynthetic pathways (see Abstract). Nowak exemplifies several amino-acid based antimicrobial agents based on this mechanism of action such as the serine derivatives shown in Figure 1 on page 3515.
The teachings of Imura are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention that the amino acids that are conjugated to the sophorolipid as demonstrated in Azim can also act as an antibacterial agent that is further enhanced as suggested by the teachings of Nowak and Imura. One of ordinary skill in the art would have this reasonable expectation because Azmi demonstrates that their amino acid – sophorolipids had antibacterial activity against both gram positive and negative organisms, Nowak provides guidance that the same amino acid based agents such as serine also have antibacterial activity, and Imura provides further guidance that sophorolipids are effective for enhancing the uptake of an active compound through skin. Therefore, an ordinary skilled artisan would have a reasonable expectation that the conjugated amino acids shown in Azim would also be enhanced by the sophorolipid compound.
Claim(s) 1 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Maeng et al. (Molecules, 2018 in PTO-892) in view of Azim et al. (Bioconjugate Chem., 2006 in IDS filed 05/18/2023) and Janni et al. (Journal of Molecular Liquids, 2021 in PTO-892).
Maeng teaches a novel microbial technique for producing high-quality sophorolipids from horse oil suitable for cosmetic applications (see Abstract). Maeng teaches effective and safe (less toxic) ingredients are required for cosmetic products (see right column page 917). Maeng teaches that biosurfactants such as sophorolipids have lower toxicity and higher biodegradability and are used widely in cosmetics and personal care products as emulsifying, foaming and wettings agents, as well as solvents, due to their excellent moisture retaining capacity (see left column page 923). Maeng further teaches that the emulsification and antibacterial properties of sophorolipids make them suitable for use in antidandruff shampoos, acne removers, and deodorants (see left column to right column page 923).
Maeng demonstrates in Fig 3-6 on pages 922-925 an in vitro human dermal fibroblast model to measure elastase inhibition activity and found that antiwrinkle properties of isolated sophorolipids were better than those of horse oil or hydrolysed horse oil in several in vitro assays. Furthermore, no cytotoxicity was observed at a concentration of 50 ug/ml, and wound-healing capacity was evident in a cell culture model. Additionally, the synthesized sophorolipids attenuated lipopolysaccharide-induced expression of inflammatory cytokines in macrophages, and efficiently inhibited several strains of bacteria and yeast (see Abstract).
The difference between Maeng and the claimed invention is that Maeng does not teach the compound of instant claim 1 and wherein the first therapeutic agent cargo is either salicylic acid or succinic acid.
The teachings of Azim are as described above and teach the compound recited in instant claim 1.
Janni teaches novel surfactant compounds based on maleic and succinic acid for potential application in personal care (see Abstract). Janni teaches their prepared surfactants depicted low critical micelle concentration (CMC) and a high adsorption efficiency, which is highly beneficial for creating personal care formulations. Janni teaches that their surfactants formed larger micelles which is important for skin care as larger micelles cannot penetrate the skin layer (see Abstract). Janni further teaches that their surfactants depicted good foamability and stability attributed to faster monomer adsorption and small bubble size which was preferred for cleansing application (see Abstract).
Janni demonstrates the synthesis of their surfactants such as sodium lauryl succinamide in Section 3.5 on page 3 and show below:
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Here, Janni demonstrates the attachment of a surfactant compound (1-dodecylamine) to a succinic acid via amide formation.
It would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the sohprolipid disclosed in Maeng with the amino acid sophorolipid conjugate disclosed in Azim and to have further substituted the amino acid in the sophorolipid conjugate of Azim with the succinic acid of Janni to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Maeng provides further guidance that sophorolipids are also useful for cosmetic formulations such as acne removers due to its emulsification and antibacterial properties, Azim establishes their sophorolipid conjugates as also having antimicrobial action due to its biosurfactant properties, and Janni provides guidance of attaching a succinic acid moiety to a similar surfactant based alkyl chain structure via amide linkage that imparted beneficial properties for cosmetic applications such as low CMC, high surface tension, good foamability and stability. Therefore, an ordinary skilled artisan could have predictable considered alternative sophorolipid compounds such as the sophorolipid conjugates of Azim with a reasonable expectation of success and would have been further motivated to conjugate succinic acid to sophorolipid to improve its biosurfactant properties for cosmetic applications such as acne remover and would have a reasonable expectation of success based on guidance of forming sophorolipid conjugate structures as shown in Azim, and attaching succinic acid to similar surfactant based alkyl compounds via amide linkage as shown in Janni.
Furthermore, instant claims 16-17 further limits what the first and second therapeutic agent cargo can be, however instant claim 1 (claim 3 depends from claim 1) only requires one therapeutic agent cargo on the compound as recited “wherein at least one of R1, R2, and R3 is a therapeutic agent cargo”. Therefore, neither instant claims 16-17 nor instant claim 1 limit the compound to having more than one therapeutic agent, so the combination of references described above meet all of the limitations of instant claims 16-17
Claim(s) 1, 18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Kwak et al. (Journal of Animal Science and Biotechnology, 2021 in PTO-892) in view of Azim et al. (Bioconjugate Chem., 2006 in IDS filed 05/18/2023).
Kwak teaches that dietary sophorolipid accelerates growth by modulation of gut microbiota population and intestinal environments in broiler chickens (see Abstract). Kwak teaches sophorolipid may increase beneficial microflora and decrease pathogenic bacteria in the gastrointestinal tract (see Abstract). Kwak teaches that the development of novel and eco-friendly materials is needed to replace antibiotic growth promoters. Additionally, Kwak teaches that various bio-surfactants have been investigated because of their antibacterial property and further teaches sophorolipid (SPL) has received much attention in various industrial fields, such as medical, hygiene, and pharmaco-dermatological areas, due to their relatively less toxicity and more biodegradability (see second paragraph left column page 2). Kwak teaches that sophorolipids have diverse biological properties including antibacterial activity, immunomodulation capacity, and stimulation of dermal fibroblasts and collagen production, which implies that sophorolipids may have potential to be applied in the animal feed industry for improving animal health and growth (see last paragraph left column page 2).
Kwak demonstrates in Table 3 on page 4 and in Fig 1-3 on pages 5-6 that sophorolipid supplementation to broiler chickens significant accelerated birds’ growth as seen by the increased bodyweight as well as significantly increased Lactobacillus spp., Akkermansia muciniphila, and cecal butyrate among all treatment groups. Furthermore, Kwak teaches that sophorolipid supplementation significantly increased villus height, ratio of villus height to crypt depth, goblet cell numbers, and the gene expression levels of claudin-1 and mucin 2 as well as significantly decreased the mRNA expression level of pro-inflammatory cytokine, interleukin-6, and increased that of anti-inflammatory cytokine, interleukin-10, compared to other treatments (see Abstract). Kwak concludes that sophorolipid supplementation in broiler feed could modulate the intestinal microbiota population and
short-chain fatty acid levels. Hence, the promoted gut environment could improve gut defense integrity, including intensified mucus layer and tight junction, and alleviate local inflammation, resulting in the acceleration of chick growth (see first paragraph under section “Conclusions” on page 8).
The difference between Kwak and the claimed invention is that Kwak does not teach the compound of instant claim 1 and wherein the first therapeutic agent cargo is either salicylic acid or succinic acid.
The teachings of Azim are as described and teach the compound recited in instant claim 1.
It would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the sophorolipid disclosed in Kwak with the sophorolipid conjugate of Azim to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Azim demonstrates that their sophorolipid conjugates have similar applications such as having anti-bacterial activity against similar pathogenic bacteria due to its biosurfactant properties. Therefore, an ordinary skilled artisan could have predictably considered using alternative sophorolipid compounds such as the sophorolipid conjugates of Azim for restoring gut health and improving weight gain with a reasonable expectation of success.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3 and 6-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-26 and 55-65 of copending Application No. 17/776,729 (‘729).
Claim 55 of ‘729 recites a sophorolipid derivative with the following structure:
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The claims of ‘729 recite R1 is H or Ac, and R2 can be
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, wherein R3 is OH or a functional group containing one or more cationic amines derived from arginine, lysine, histidine, and/or glycine amino acids. Claim 56 of ‘729 recites the R3 structure when R2 is a) is the following:
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Here, the R3 functional group meet the limitation of a therapeutic acid cargo linked via an amide linkage. Claim 62 of ‘729 recites the cationic sophorolipid derivative can be a cleaning product, a personal care product, a cosmetic product, and among others. Claim 61 of ‘729 recites a method of disinfecting a surface that is infected with a deleterious microorganism by applying a composition comprising the sophorolipid derivative.
It would have been prima facie obvious before the effective filing date of the claimed invention to select from within the genus of the recited sophorolipid in ‘729 to arrive at the instant invention because the claims of ‘729 recites a finite list of substituents for the sophorolipid derivative such that an ordinary skilled artisan could readily arrive at the instant invention.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 9-10, 12-13, and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-26 and 55-65 of copending Application No. 17/776,729 (‘729) in view of Zerkowski et al. (Journal of Surfactants and Detergents, 2006 in IDS filed on 02/05/2025) and Azim et al. (Bioconjugate Chem., 2006 in IDS filed 05/18/2023).
The claims of ‘729 are as recited above, and recite the compound of instant claim 1.
The difference between the claims of ‘729 and the instant invention is that the claims of ‘729 do not recite at least one of R2 and R3 is the second therapeutic agent cargo.
The independent teachings of Azim and Zerkowski are described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the sophorolipd recited in the claims of ‘729 by further attaching an animo acid at the R2 position as demonstrated by Zerkowski with further guidance from Azim to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Zerkowski provides guidance of modifying these sophorolipids to increase its utility as a surfactant by conjugating an amino acid group on the R2 using via Paba linker (ester linkage), and Azim provides guidance of using sophorolipids as anti-microbial agents due to its biosurfactant properties and demonstrates this use with similar amino-acid conjugated sophorolipid derivatives. Therefore, an ordinary skilled artisan could have predictably considered conjugating the R2 position with an amino acid as demonstrated in Zerkowski, and would have been further motivated to do so in order to increase its surfactant properties.
In regards to instant claims 12-13, it would have also been prima facie obvious before the effective filing date of the claimed invention to make the R1 position of the sophorolipid conjugate as recited by the combination of the claims of ‘729 and the teachings of Azim and Zerkowski described above unmodified to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Zerkowski provides guidance of amino acid – sophorolipid conjugates that are only modified at the R2 position. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of amino acid modification sites with a reasonable expectation of success.
In regards to instant claim 19, it would have also been prima facie before the effective filing date of the claimed invention to have administered the modified sophorolipid conjugates as recited by the combination of the claims of ‘729 and the teachings of Zerkowski and Azim described above to a subject in order reduce pathogenic gram-negative bacteria in the microbiome of the subject because Azim demonstrates that their conjugates had antibacterial activity against gram negative organisms.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 4 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-26 and 55-65 of copending Application No. 17/776,729 (‘729) in view of Zerkowski et al. (Journal of Surfactants and Detergents, 2006 in IDS filed on 02/05/2025), Azim et al. (Bioconjugate Chem., 2006 in IDS filed 05/18/2023), and Imura et al. (Journal of Oleo Science in IDS filed on 05/18/2023)
The combination of the claims of ‘729 and the teachings of Zerkowski and Azim are as recited above, and recite the compound of instant claim 1.
The combined references, however, do not recite wherein X is O- and R1 is sodium
The independent teaching of Imura is as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the sophorolipid derivative as recited by the combination of the claims of ‘729 and the teachings of Zerkowski and Azim described above by forming a sodium salt of the sophorolipid as demonstrated in Imura to arrive at the claimed invention. One of ordinary skill would have been motivated to make this modification with a reasonable expectation of success because Imura provides guidance of using sodium salt sophorolipids as a skin penetration enhancer due to its biosurfactant properties. Therefore, an ordinary skilled artisan could have chosen from a finite number of predictable solutions of sodium salt sophorolipids useful for the same biosurfactant properties with a reasonable expectation of success.
In regards to instant claim 15, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered as recited by the combination of the claims of ‘729 and the teachings of Zerkowski, Azim, and Imura described above described above to a subject to improve the dermal penetrability of an active ingredient as demonstrated in Imura to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Imura demonstrates that their sophorolipids can be used as a skin penetration enhancer for an active ingredient.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 16-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-26 and 55-65 of copending Application No. 17/776,729 (‘729) in view of Janni et al. (Journal of Molecular Liquids, 2021 in PTO-892), Azim et al. (Bioconjugate Chem., 2006 in IDS filed 05/18/2023), and Maeng et al. (Molecules, 2018 in PTO-892).
The claims of ‘729 are as recited above, and recite the compound of instant claim 1.
The difference between the claims of ‘729 and the instant invention is that the claims of ‘729 do not recite a method of treating a skin condition such as acne and wherein the therapeutic agent cargo is succinic acid.
The independent teachings of Azim, Janni, and Maeng are described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have substituted the amino acid in the sophorolipid derivative as recited in the claims of ‘729 with the succinic acid of Janni with further guidance from Azim and to further use this modified conjugate for treating a skin condition such as acne as suggested by Maeng to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to make these modifications with a reasonable expectation of success because Janni provides guidance of attaching a succinic acid moiety to a similar surfactant based alkyl chain structure via amide linkage that imparted beneficial properties for cosmetic applications such as low CMC, high surface tension, good foamability and stability, Azim establishes forming similar sophorolipid conjugates as having various antimicrobial action due to its biosurfactant properties, and Maeng provides further guidance that sophorolipids are also useful for cosmetic formulations such as acne removers due to its emulsification and antibacterial properties. Therefore, an ordinary skilled artisan would have been motivated to conjugate succinic acid to sophorolipid to further improve its biosurfactant properties for cosmetic applications such as acne remover and would have a reasonable expectation of success based on guidance of attaching succinic acid to similar surfactant based alkyl compounds via amide linkage as shown in Janni and forming sophorolipid conjugate structures as shown in Azim.
Furthermore, instant claims 16-17 further limits what the first and second therapeutic agent cargo can be, however instant claim 1 (claim 3 depends from claim 1) only requires one therapeutic agent cargo on the compound as recited “wherein at least one of R1, R2, and R3 is a therapeutic agent cargo”. Therefore, neither instant claims 16-17 nor instant claim 1 limit the compound to having more than one therapeutic agent, so the combination of references described above meet all of the limitations of instant claims 16-17.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 18, and 20 are provisionally rejected on the groun